Personalized deep learning of individual immunopeptidomes to identify neoantigens for cancer vaccines

Tumour-specific neoantigens play a major role for developing personal vaccines in cancer immunotherapy. We propose a personalized de novo peptide sequencing workflow to identify HLA-I and HLA-II neoantigens directly and solely from mass spectrometry data. Our workflow trains a personal deep learning model on the immunopeptidome of an individual patient and then uses it to predict mutated neoantigens of that patient. This personalized learning and mass spectrometry-based approach enables comprehensive and accurate identification of neoantigens. We applied the workflow to datasets of five patients with melanoma and expanded their predicted immunopeptidomes by 5–15%. Subsequently, we discovered neoantigens of both HLA-I and HLA-II, including those with validated T-cell responses and those that had not been reported in previous studies. Neoantigens play a critical role in cancer immunotherapy. Tran et al. show how training a personalized deep learning model for each individual patient can improve the accuracy and identification rate of mutated neoantigens.